Epalrestat

Approved Indications:

• Diabetic Neuropathy:
• Symptomatic treatment of diabetic peripheral neuropathy in patients with type 2 diabetes mellitus.
• Reduces neuropathic pain, numbness, and tingling sensations.
• May help improve nerve conduction velocity.

Off-Label / Clinically Accepted Uses:

• Occasionally used in early-stage diabetic neuropathy to prevent progression of nerve damage.
• Investigational use in other diabetic microvascular complications, though evidence remains limited.

Adults:

• Standard dose: 50 mg orally, three times daily immediately after meals.
• Swallow tablets whole with water.

Special Populations:

• Renal Impairment: Caution in severe renal impairment (creatinine clearance <30 mL/min). Dose adjustment may be required.
• Hepatic Impairment: Limited data; use cautiously.
• Elderly: No specific dose adjustment required; monitor tolerability.

Pediatrics: Safety and efficacy not established; not recommended.

Duration: Continuous therapy as long as symptomatic benefit persists; evaluate efficacy periodically.

Epalrestat is an aldose reductase inhibitor. In hyperglycemic states, excess glucose is converted to sorbitol via the polyol pathway in nerves, leading to osmotic stress, oxidative damage, and nerve dysfunction. Epalrestat inhibits aldose reductase, reducing sorbitol accumulation in peripheral nerves. This decreases osmotic stress, oxidative damage, and inflammation, thereby improving nerve function and alleviating neuropathic symptoms.

• Absorption: Rapid oral absorption; peak plasma concentration in 1–2 hours.
• Bioavailability: Moderate; food slightly delays absorption but does not significantly affect extent.
• Distribution: Widely distributed; protein binding ~95%.
• Metabolism: Primarily hepatic, via glucuronidation; minor metabolism through oxidative pathways.
• Elimination: Excreted mainly in urine as metabolites.
• Half-Life: Approximately 1.5–2 hours.
• Onset of Action: Clinical improvements in neuropathic symptoms typically observed within 4–8 weeks.

• Pregnancy: No well-controlled studies in humans; use only if potential benefit justifies risk. Animal studies show limited adverse effects.
• Lactation: Unknown excretion in human milk; caution advised. Avoid use during breastfeeding unless benefits outweigh risks.
• Note: Limited clinical data; careful monitoring recommended.

• Primary Class: Antidiabetic agent (Peripheral neuropathy management)
• Subclass: Aldose reductase inhibitor

• Known hypersensitivity to epalrestat or any excipients.
• Severe hepatic dysfunction.
• Severe renal impairment without careful monitoring.

• Liver Function: Monitor liver enzymes during therapy; rare hepatotoxicity reported.
• Renal Function: Use caution in patients with impaired renal function.
• Allergic Reactions: Rare hypersensitivity reactions may occur; discontinue if severe rash, itching, or edema develops.
• High-Risk Groups: Elderly patients should be monitored for tolerability and adverse effects.

Common Adverse Effects:

• Gastrointestinal: nausea, diarrhea
• Neurological: headache, dizziness
• Musculoskeletal: joint pain

Serious or Rare Adverse Effects:

• Hepatic dysfunction (elevated ALT/AST)
• Allergic reactions: rash, urticaria
• Rare gastrointestinal discomfort or fatigue

Timing and Severity:

• Most side effects are mild and transient; typically occur within the first few weeks of therapy.

• Antidiabetic Agents: Additive effect with insulin or oral hypoglycemics; monitor for hypoglycemia.
• Hepatic Metabolized Drugs: Potential interaction with drugs undergoing glucuronidation; clinical significance limited.
• Food: No clinically significant interactions.

• Clinical Guidelines: Recommended as first-line pharmacologic therapy for symptomatic diabetic neuropathy in type 2 diabetes patients, particularly in Japan and several Asian countries.
• Safety Updates: Reinforced monitoring of liver function; caution advised in patients with existing hepatic impairment.
• Regulatory Status: Approved for use in diabetic neuropathy; no major recent changes in dosing or indications.

• Temperature: Store at 20°C–25°C (68°F–77°F); short excursions 15°C–30°C allowed.
• Humidity & Light: Protect from moisture and direct light.
• Handling: Keep tablets in original container; do not crush or break.
• Reconstitution: Not applicable; oral tablets ready for administration.